The objective of this proposal is to create a new high-throughput screening (HTS) facility at Stanford University. Recent advances in genetics and chemical synthesis have fostered novel strategies for biomedical research, and high-throughput liquid-handling and data acquisition instrumentation will enable Stanford faculty and students to exploit these new scientific approaches. For example, the sequencing of entire genomes and the development of techniques to selectively alter gene expression now permit the rapid functional evaluation of essentially any gene product. The screening of natural products and synthetic chemicals for biologically active compounds is also emerging as a powerful complementary approach for deciphering biological processes. The proposed Biomek FX robotic liquid-handling workstation and EnVision multi-label microplate reader will constitute the primary instrumentation systems of this facility, and with this equipment, Stanford researchers will be able to conduct systematic and comprehensive screens of biological systems involving genetic and/or chemical perturbations. Possible approaches include the use of: (1) cDNA libraries for in vivo or in vitro protein expression; (2) siRNA libraries for targeted 'knock-downs' of protein expression; and (3) chemical libraries for the identification of small molecule modulators of specific biological processes. The proposed HTS facility will be developed and managed by the Department of Molecular Pharmacology, and the research projects specifically outlined in this proposal involve studies by its faculty members that pertain to cardiac hypertrophy, neuronal function, drug delivery strategies, embryonic signaling pathways, and mechanisms of oncogenesis. It should be emphasized, however, that these investigations are merely representative of the diverse research activities that the HTS facility will support. Available to the entire Stanford research community and its neighboring institutions, the proposed instrumentation will broadly advance our molecular and cellular understanding of human health and disease by promoting the use of genome-wide approaches in the biomedical sciences and the advancement of chemical biology research.